In this chapter we discuss the design, delivery and preclinical testing of
mutation-specific ribozymes for the treatment of dominantly inherited retin
al disease. We focus particular attention on the initial screening of riboz
ymes in vitro, because the activity of RNA enzymes in cell-free systems can
be used to predict their suitability for animal experiments. Current techn
iques for delivering genes of Interest to cells of the retina using viral v
ectors are then briefly surveyed emphasizing vector properties that best ma
rch to the needs of a ribozyme-based therapy. Using these considerations, a
nalysis of ribozyme gene therapy for an autosomal dominant RP-like disease
in a rodent model is outlined emphasizing the desirability of combining bio
chemical, morphological and electrophysiological measures of therapy. Final
ly, we describe alternative. perhaps more general, ribozyme approaches that
have yet to be tested in the context of retinal disease. (C) 2000 Publishe
d by Elsevier Science Ltd.